Agents which accelerate fetal lung maturation may be useful clinically for the prevention of the Respiratory Distress Syndrome of the newborn (RDS). Organ culture of fetal rat lung will be used as a model to investigate the influence of cortisol, thyroxine and cyclic AMP on the biosynthesis of the pulmonary phospholipids in order to elucidate their effect on lung maturation. The pathogenesis of the increased incidence of RDS in infants born to diabetic mothers will be studied by examining the effect of insulin on lung phospholipid and carbohydrate metabolism. The ontogeny of the response to these hormones will also be determined. Phospholipid and glycogen biosynthesis will be studied by measuring the incorporation of labeled precursors into phospholipid and glycogen isolated from the explants, and by assaying the activity of enzymes related to lung fatty acid, phospholipid and glycogen synthesis. Net content of phospholipid and glycogen in the explants will also be determined. Parallel light and electron microscopic studies will provide information on the morphologic effects of these agents on developing lung. Further information on the basic mechanisms of action of hormones which accelerate fetal lung maturation is required before their clinical use becomes widespread. The organ culture model is a particularly useful system for the study of hormonal action on developing tissues.